The Experts below are selected from a list of 291843 Experts worldwide ranked by ideXlab platform
Peixin Yang - One of the best experts on this subject based on the ideXlab platform.
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oxidative stress induced mir 27a targets the redox gene Nuclear Factor erythroid 2 related Factor 2 in diabetic embryopathy
American Journal of Obstetrics and Gynecology, 2018Co-Authors: Yang Zhao, Daoyin Dong, Albert E Reece, Ashley R Wang, Peixin YangAbstract:Background Maternal diabetes induces neural tube defects, and oxidative stress is a causal Factor for maternal diabetes–induced neural tube defects. The redox gene Nuclear Factor erythroid 2-related Factor 2 is the master regulator of the cellular antioxidant system. Objective In this study, we aimed to determine whether maternal diabetes inhibits Nuclear Factor erythroid 2-related Factor 2 expression and Nuclear Factor erythroid 2-related Factor 2–controlled antioxidant genes through the redox-sensitive miR-27a. Study Design We used a well-established type 1 diabetic embryopathy mouse model induced by streptozotocin for our in vivo studies. Embryos at embryonic day 8.5 were harvested for analysis of Nuclear Factor erythroid 2-related Factor 2, Nuclear Factor erythroid 2-related Factor 2–controlled antioxidant genes, and miR-27a expression. To determine if mitigating oxidative stress inhibits the increase of miR-27a and the decrease of Nuclear Factor erythroid 2-related Factor 2 expression, we induced diabetic embryopathy in superoxide dismutase 2 (mitochondrial-associated antioxidant gene)-overexpressing mice. This model exhibits reduced mitochondria reactive oxygen species even in the presence of hyperglycemia. To investigate the causal relationship between miR-27a and Nuclear Factor erythroid 2-related Factor 2 in vitro, we examined C17.2 neural stem cells under normal and high-glucose conditions. Results We observed that the messenger RNA and protein levels of Nuclear Factor erythroid 2-related Factor 2 were significantly decreased in embryos on embryonic day 8.5 from diabetic dams compared to those from nondiabetic dams. High-glucose also significantly decreased Nuclear Factor erythroid 2-related Factor 2 expression in a dose- and time-dependent manner in cultured neural stem cells. Our data revealed that miR-27a was up-regulated in embryos on embryonic day 8.5 exposed to diabetes, and that high glucose increased miR-27a levels in a dose- and time-dependent manner in cultured neural stem cells. In addition, we found that a miR-27a inhibitor abrogated the inhibitory effect of high glucose on Nuclear Factor erythroid 2-related Factor 2 expression, and a miR-27a mimic suppressed Nuclear Factor erythroid 2-related Factor 2 expression in cultured neural stem cells. Furthermore, our data indicated that the Nuclear Factor erythroid 2-related Factor 2–controlled antioxidant enzymes glutamate-cysteine ligase catalytic subunit, glutamate-cysteine ligase modifier subunit, and glutathione S-transferase A1 were down-regulated by maternal diabetes in embryos on embryonic day 8.5 and high glucose in cultured neural stem cells. Inhibiting miR-27a restored expression of glutamate-cysteine ligase catalytic subunit, glutamate-cysteine ligase modifier subunit, and glutathione S-transferase A1. Overexpressing superoxide dismutase 2 reversed the maternal diabetes–induced increase of miR-27a and suppression of Nuclear Factor erythroid 2-related Factor 2 and Nuclear Factor erythroid 2-related Factor 2–controlled antioxidant enzymes. Conclusion Our study demonstrates that maternal diabetes–induced oxidative stress increases miR-27a, which, in turn, suppresses Nuclear Factor erythroid 2-related Factor 2 and its responsive antioxidant enzymes, resulting in diabetic embryopathy.
Preet M Chaudhary - One of the best experts on this subject based on the ideXlab platform.
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the ectodermal dysplasia receptor activates the Nuclear Factor kappab jnk and cell death pathways and binds to ectodysplasin a
Journal of Biological Chemistry, 2001Co-Authors: Arvind Kumar, Michael T Eby, Suwan K Sinha, Alan Jasmin, Preet M ChaudharyAbstract:The ectodermal dysplasia receptor (EDAR) is a recently isolated member of the tumor necrosis Factor receptor family that has been shown to play a key role in the process of ectodermal differentiation. We present evidence that EDAR is capable of activating the Nuclear Factor-kappaB, JNK, and caspase-independent cell death pathways and that these activities are impaired in mutants lacking its death domain or those associated with anhidrotic ectodermal dysplasia and the downless phenotype. Although EDAR possesses a death domain, it did not interact with the death domain-containing adaptor proteins TRADD and FADD. EDAR successfully interacted with various TRAF family members; however, a dominant-negative mutant of TRAF2 was incapable of blocking EDAR-induced Nuclear Factor-kappaB or JNK activation. Collectively, the above results suggest that EDAR utilizes a novel signal transduction pathway. Finally, ectodysplasin A can physically interact with the extracellular domain of EDAR and thus represents its biological ligand.
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the ectodermal dysplasia receptor activates the Nuclear Factor κb jnk and cell death pathways and binds to ectodysplasin a
Journal of Biological Chemistry, 2001Co-Authors: Arvind Kumar, Michael T Eby, Suwan K Sinha, Alan Jasmin, Preet M ChaudharyAbstract:The ectodermal dysplasia receptor (EDAR) is a recently isolated member of the tumor necrosis Factor receptor family that has been shown to play a key role in the process of ectodermal differentiation. We present evidence that EDAR is capable of activating the Nuclear Factor-kappaB, JNK, and caspase-independent cell death pathways and that these activities are impaired in mutants lacking its death domain or those associated with anhidrotic ectodermal dysplasia and the downless phenotype. Although EDAR possesses a death domain, it did not interact with the death domain-containing adaptor proteins TRADD and FADD. EDAR successfully interacted with various TRAF family members; however, a dominant-negative mutant of TRAF2 was incapable of blocking EDAR-induced Nuclear Factor-kappaB or JNK activation. Collectively, the above results suggest that EDAR utilizes a novel signal transduction pathway. Finally, ectodysplasin A can physically interact with the extracellular domain of EDAR and thus represents its biological ligand.
Gilberto Velho - One of the best experts on this subject based on the ideXlab platform.
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clinical spectrum associated with hepatocyte Nuclear Factor 1β mutations
Annals of Internal Medicine, 2004Co-Authors: C Bellannechantelot, Dominique Chauveau, Jeanfrancois Gautier, Daniele Duboislaforgue, Severine Clauin, Sandrine Beaufils, Jeanmarie Wilhelm, Christian Boitard, Laurehelene Noel, Gilberto VelhoAbstract:Maturity-onset diabetes of the young type 5 encompasses a wide clinical spectrum of defects in organogenesis, which are related to specific mutations in hepatocyte Nuclear Factor-1β. Nonobese patie...
Arthur S Aylsworth - One of the best experts on this subject based on the ideXlab platform.
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deletion of hepatocyte Nuclear Factor 1 beta in an infant with prune belly syndrome
American Journal of Perinatology, 2010Co-Authors: Sina Haeri, Patricia Devers, Kathleen Kaiserrogers, Vincent J Moylan, Beth S Torchia, Amanda L Horton, Honor M Wolfe, Arthur S AylsworthAbstract:Prune belly syndrome is a rare congenital disorder characterized by deficiency of abdominal wall muscles, cryptorchidism, and urinary tract anomalies. We have had the opportunity to study a baby with prune belly syndrome associated with an apparently de novo 1.3-megabase interstitial 17q12 microdeletion that includes the hepatocyte Nuclear Factor-1-beta gene at 17q12. One previous patient, an adult, has been reported with prune belly syndrome and a hepatocyte Nuclear Factor-1-beta microdeletion. Hepatocyte Nuclear Factor-1-beta is a widely expressed transcription Factor that regulates tissue-specific gene expression and is expressed in numerous tissues including mesonephric duct derivatives, the renal tubule of the metanephros, and the developing prostate of the mouse. Mutations in hepatocyte Nuclear Factor-1-beta cause the "renal cysts and diabetes syndrome," isolated renal cystic dysplasia, and a variety of other malformations. Based on its expression pattern and the observation of two affected cases, we propose that haploinsufficiency of hepatocyte Nuclear Factor-1-beta may be causally related to the production of the prune belly syndrome phenotype through a mechanism of prostatic and ureteral hypoplasia that results in severe obstructive uropathy with urinary tract and abdominal distension.
Kevin Colclough - One of the best experts on this subject based on the ideXlab platform.
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mutations in the genes encoding the transcription Factors hepatocyte Nuclear Factor 1 alpha hnf1a and 4 alpha hnf4a in maturity onset diabetes of the young
Human Mutation, 2006Co-Authors: Sian Ellard, Kevin ColcloughAbstract:Maturity-onset diabetes of the young (MODY) is a monogenic form of diabetes mellitus characterized by autosomal dominant inheritance, early age of onset (often <25 years of age), and pancreatic beta-cell dysfunction. MODY is both clinically and genetically heterogeneous, with six different genes identified to date; glucokinase (GCK), hepatocyte Nuclear Factor-1 alpha (HNF1A, or TCF1), hepatocyte Nuclear Factor-4 alpha (HNF4A), insulin promoter Factor-1 (IPF1 or PDX1), hepatocyte Nuclear Factor-1 beta (HNF1B or TCF2), and neurogenic differentiation 1 (NEUROD1). Mutations in the HNF1A gene are a common cause of MODY in the majority of populations studied. A total of 193 different mutations have been described in 373 families. The most common mutation is Pro291fs (P291fsinsC) in the polycytosine (poly C) tract of exon 4, which has been reported in 65 families. HNF4A mutations are rarer; 31 mutations reported in 40 families. Sensitivity to treatment with sulfonylurea tablets is a feature of both HNF1A and HNF4A mutations. The identification of an HNF1A or 4A gene mutation confirms a diagnosis of MODY and has important implications for clinical management.
